International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Pediatric Sepsis in General Emergency Departments: Association Between Pediatric Sepsis Case Volume, Care Quality, and Outcome.

STUDY OBJECTIVE: To assess whether a general emergency department's (ED) annual pediatric sepsis volume increases the odds of delivering care concordant with Surviving Sepsis pediatric guidelines. METHODS: A retrospective cohort study of children <18 years with sepsis presenting to 29 general EDs. Emergency department and hospital data were abstracted from the medical records of 2 large health care systems, including all hospitals to which children were transferred. Guideline-concordant care was defined as intravenous antibiotics within 3 hours, intravenous fluid bolus within 3 hours, and lactate measured. The association between annual ED pediatric sepsis encounters and the probability of receiving guideline-concordant care was assessed. RESULTS: We included 1,527 ED encounters between January 1, 2015, and September 30, 2021. Three hundred and one (19%) occurred in 25 EDs with <10 pediatric sepsis encounters annually, 466 (31%) in 3 EDs with 11 to 100 pediatric sepsis encounters annually, and 760 (50%) in an ED with more than 100 pediatric sepsis encounters annually. Care was concordant in 627 (41.1%) encounters. In multivariable analysis, annual pediatric sepsis volume was minimally associated with the probability of guideline-concordant care (odds ratio 1.002 [95% confidence interval 1.001 to 1.00]). Care concordance increased from 23.1% in 2015 to 52.8% in 2021. CONCLUSION: Guideline-concordant sepsis care was delivered in 41% of pediatric sepsis cases in general EDs, and annual ED pediatric sepsis encounters had minimal association with the odds of concordant care. Care concordance improved over time. This study suggests that factors other than pediatric sepsis volume are important in driving care quality and identifying drivers of improvement is important for children first treated in general EDs.

Impact of Time-to-Antibiotic Delivery in Pediatric Patients With Cancer Presenting With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) in pediatric patients with cancer can cause severe infections, and prompt antibiotics are warranted. Extrapolated from other populations, a time-to-antibiotic (TTA) metric of <60 minutes after medical center presentation was established, with compliance data factoring into pediatric oncology program national rankings. METHODS: All FN episodes occurring at Vanderbilt Children's Hospital (2007-February 2022) and a sample of episodes from Colorado Children's Hospital (2012-2019) were abstracted, capturing TTA and clinical outcomes including major complications (intensive care unit [ICU] admission, vasopressors, intubation, or infection-related mortality). Odds ratios (ORs) were adjusted for age, treatment center, absolute neutrophil count, hypotension presence, stem-cell transplant status, and central line type. RESULTS: A total of 2,349 episodes were identified from Vanderbilt (1,920) and Colorado (429). Only 0.6% (n = 14) episodes required immediate ICU management, with a median TTA of 28 minutes (IQR, 20-37). For the remaining patients, the median TTA was 56 minutes (IQR, 37-90), and 54.3% received antibiotics in <60 minutes. There were no significant associations between TTA (<60 or ≥60 minutes) and major complications (adjusted OR, 0.99 [95% CI, 0.62 to 1.59]; P = .98), and a TTA ≥60 minutes was not associated with any type of complication. Similarly, TTA, when evaluated as a continuous variable, was not associated with a major (OR, 0.99 [95% CI, 0.94 to 1.04]; P = .69) nor any other complication in adjusted analysis. CONCLUSION: There is no clear evidence that a reduced TTA improves clinical outcomes in pediatric oncology FN and thus it should not be used as a primary quality measure.

Serum lactate is associated with increased illness severity in immunocompromised pediatric hematology oncology patients presenting to the emergency department with fever.

Introduction: Determining which febrile pediatric hematology/oncology (PHO) patients will decompensate from severe infection is a significant challenge. Serum lactate is a well-established marker of illness severity in general adult and pediatric populations, however its utility in PHO patients is unclear given that chemotherapy, organ dysfunction, and cancer itself can alter lactate metabolism. In this retrospective analysis, we studied the association of initial serum lactate in febrile immunosuppressed PHO patients with illness severity, defined by the incidence of clinical deterioration events (CDE) and invasive bacterial infection (IBI) within 48 hours. Methods: Receiver operating characteristic (ROC) curves were reported using initial lactate within two hours of arrival as the sole predictor for CDE and IBI within 48 hours. Using a generalized estimating equations (GEE) approach, the association of lactate with CDE and IBI within 48 hours was tested in univariate and multivariable analyses including covariates based on Quasi-likelihood under Independence Model Criterion (QIC). Additionally, the association of lactate with secondary outcomes (i.e., hospital length of stay (LOS), intensive care unit (PICU) admission, PICU LOS, non-invasive infection) was assessed. Results: Among 897 encounters, 48 encounters had ≥1 CDE (5%), and 96 had ≥1 IBI (11%) within 48 hours. Elevated lactate was associated with increased CDE in univariate (OR 1.77, 95%CI: 1.48-2.12, p<0.001) and multivariable (OR 1.82, 95%CI: 1.43-2.32, p<0.001) analyses, longer hospitalization (OR 1.15, 95%CI: 1.07-1.24, p<0.001), increased PICU admission (OR 1.68, 95%CI: 1.41-2.0, p<0.001), and longer PICU LOS (OR 1.21, 95%CI: 1.04-1.4, p=0.01). Elevated lactate was associated with increased IBI in univariate (OR 1.40, 95%CI: 1.16-1.69, p<0.001) and multivariable (OR 1.49, 95%CI: 1.23-1.79, p<0.001) analyses. Lactate level was not significantly associated with increased odds of non-invasive infection (p=0.09). The QIC of the model was superior with lactate included for both CDE (305 vs. 325) and IBI (563 vs. 579). Conclusions: These data demonstrated an independent association of elevated initial lactate level and increased illness severity in febrile PHO patients, suggesting that serum lactate could be incorporated into future risk stratification strategies for this population.

"These Are Our Kids": Qualitative Interviews With Clinical Leaders in General Emergency Departments on Motivations, Processes, and Guidelines in Pediatric Sepsis Care.

STUDY OBJECTIVE: Sepsis is a leading cause of pediatric death requiring emergency resuscitation. Most children with sepsis are treated in general emergency departments (EDs); however, research has focused on pediatric EDs. We sought to identify barriers and facilitators to pediatric sepsis care in general EDs, including care processes, the role of guidelines, and incentivized metrics. METHODS: In this qualitative study, we conducted semistructured interviews with key informant physician and nurse leaders overseeing pediatric sepsis in general EDs in 2021, including medical directors, nurse managers, and quality coordinators. Interviews were audio-recorded, transcribed, and coded using deductive domains based on steps of sepsis care, pediatric readiness, and structural dynamics. Domains were analyzed across interviews in matrices, using thematic analysis within domains. RESULTS: Twenty-one clinical leaders representing 26 hospitals, including trauma levels I to IV, were interviewed. The themes included the following: (1) motivation to improve pediatric sepsis care based on moral imperative and location; (2) need for actionable pediatric sepsis guidelines; (3) children's hospitals' role in education, protocols, transfer, and consultation; and (4) mixed feelings about reportable metrics, particularly in EDs with low pediatric volume. Sepsis care process challenges included diagnosis, intravenous access, and antibiotic delivery but varied among hospitals. CONCLUSION: Leaders in general EDs were motivated to provide high-quality pediatric sepsis care but disagreed on whether reportable metrics would drive improvements. They universally sought direct support from their nearest children's hospitals and actionable guidelines. Efforts to address pediatric sepsis quality in general EDs should prioritize guideline design, responsive pediatric transfer and consultation systems, and locally specific process improvement.

Machine Learning Approach to Predicting Absence of Serious Bacterial Infection at PICU Admission.

BACKGROUND AND OBJECTIVES: Serious bacterial infection (SBI) is common in the PICU. Antibiotics can mitigate associated morbidity and mortality but have associated adverse effects. Our objective is to develop machine learning models able to identify SBI-negative children and reduce unnecessary antibiotics. METHODS: We developed models to predict SBI-negative status at PICU admission using vital sign, laboratory, and demographic variables. Children 3-months to 18-years-old admitted to our PICU, between 2011 and 2020, were included if evaluated for infection within 24-hours, stratified by documented antibiotic exposure in the 48-hours prior. Area under the receiver operating characteristic curve (AUROC) was the primary model accuracy measure; secondarily, we calculated the number of SBI-negative children subsequently provided antibiotics in the PICU identified as low-risk by each model. RESULTS: A total of 15 074 children met inclusion criteria; 4788 (32%) received antibiotics before PICU admission. Of these antibiotic-exposed patients, 2325 of 4788 (49%) had an SBI. Of the 10 286 antibiotic-unexposed patients, 2356 of 10 286 (23%) had an SBI. In antibiotic-exposed children, a radial support vector machine model had the highest AUROC (0.80) for evaluating SBI, identifying 48 of 442 (11%) SBI-negative children provided antibiotics in the PICU who could have been spared a median 3.7 (interquartile range 0.9-9.0) antibiotic-days per patient. In antibiotic-unexposed children, a random forest model performed best, but was less accurate overall (AUROC 0.76), identifying 33 of 469 (7%) SBI-negative children provided antibiotics in the PICU who could have been spared 1.1 (interquartile range 0.9-3.7) antibiotic-days per patient. CONCLUSIONS: Among children who received antibiotics before PICU admission, machine learning models can identify children at low risk of SBI and potentially reduce antibiotic exposure.

Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock.

STUDY OBJECTIVE: To determine whether the receipt of more than or equal to 30 mL/kg of intravenous fluid in the first hour after emergency department (ED) arrival is associated with sepsis-attributable mortality among children with hypotensive septic shock. METHODS: This is a retrospective cohort study set in 57 EDs in the Improving Pediatric Sepsis Outcomes quality improvement collaborative. Patients less than 18 years of age with hypotensive septic shock who received their first intravenous fluid bolus within 1 hour of arrival at the ED were propensity-score matched for probability of receiving more than or equal to 30 mL/kg in the first hour. Sepsis-attributable mortality was compared. We secondarily evaluated the association between the first-hour fluid volume and sepsis-attributable mortality in all children with suspected sepsis in the first hour after arrival at the ED, regardless of blood pressure. RESULTS: Of the 1,982 subjects who had hypotensive septic shock and received a first fluid bolus within 1 hour of arrival at the ED, 1,204 subjects were propensity matched. In the matched patients receiving more than or equal to 30 mL/kg of fluid, 26 (4.3%) of 602 subjects had 30-day sepsis-attributable mortality compared with 25 (4.2%) of 602 receiving less than 30 mL/kg (odds ratio 1.04, 95% confidence interval 0.59 to 1.83). Among the patients with suspected sepsis regardless of blood pressure, 30-day sepsis-attributable mortality was 3.0% in those receiving more than or equal to 30 mL/kg versus 2.0% in those receiving less than 30 ml/kg (odds ratio 1.52, 95% confidence interval 0.95 to 2.44.) CONCLUSION: In children with hypotensive septic shock receiving a timely first fluid bolus within the first hour of ED care, receiving more than or equal to 30 mL/kg of bolus intravenous fluids in the first hour after arrival at the ED was not associated with mortality compared with receiving less than 30 mL/kg.

Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Third International Consensus Definitions for Sepsis and Septic Shock Definitions in the Pediatric Emergency Department.

Importance: Pediatric sepsis definitions have evolved, and some have proposed using the measure used in adults to quantify organ dysfunction, a Sequential Organ Failure Assessment (SOFA) score of 2 or more in the setting of suspected infection. A pediatric adaptation of SOFA (pSOFA) showed excellent discrimination for mortality in critically ill children but has not been evaluated in an emergency department (ED) population. Objective: To delineate test characteristics of the pSOFA score for predicting in-hospital mortality among (1) all patients and (2) patients with suspected infection treated in pediatric EDs. Design, Setting, and Participants: This retrospective cohort study took place from January 1, 2012, to January 31, 2020 in 9 US children's hospitals included in the Pediatric Emergency Care Applied Research Network (PECARN) Registry. The data was analyzed from February 1, 2020, to April 18, 2022. All ED visits for patients younger than 18 years were included. Exposures: ED pSOFA score was assigned by summing maximum pSOFA organ dysfunction components during ED stay (each 0-4 points). In the subset with suspected infection, visit meeting criteria for sepsis (suspected infection with a pSOFA score of 2 or more) and septic shock (suspected infection with vasoactive infusion and serum lactate level >18.0 mg/dL) were identified. Main Outcomes and Measures: Test characteristics of pSOFA scores of 2 or more during the ED stay for hospital mortality. Results: A total of 3 999 528 (female, 47.3%) ED visits were included. pSOFA scores ranged from 0 to 16, with 126 250 visits (3.2%) having a pSOFA score of 2 or more. pSOFA scores of 2 or more had sensitivity of 0.65 (95% CI, 0.62-0.67) and specificity of 0.97 (95% CI, 0.97-0.97), with negative predictive value of 1.0 (95% CI, 1.00-1.00) in predicting hospital mortality. Of 642 868 patients with suspected infection (16.1%), 42 992 (6.7%) met criteria for sepsis, and 374 (0.1%) met criteria for septic shock. Hospital mortality rates for suspected infection (599 502), sepsis (42 992), and septic shock (374) were 0.0%, 0.9%, and 8.0%, respectively. The pSOFA score had similar discrimination for hospital mortality in all ED visits (area under receiver operating characteristic curve, 0.81; 95% CI, 0.79-0.82) and the subset with suspected infection (area under receiver operating characteristic curve, 0.82; 95% CI, 0.80-0.84). Conclusions and Relevance: In a large, multicenter study of pediatric ED visits, a pSOFA score of 2 or more was uncommon and associated with increased hospital mortality yet had poor sensitivity as a screening tool for hospital mortality. Conversely, children with a pSOFA score of 2 or less were at very low risk of death, with high specificity and negative predictive value. Among patients with suspected infection, patients with pSOFA-defined septic shock demonstrated the highest mortality.

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce.

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

Confidence-weighted Testing as an Impactful Education Intervention within a Pediatric Sepsis Quality Improvement Initiative.

INTRODUCTION: Confidence-weighted testing assesses learners' beliefs about their knowledge and skills. As part of a hospital-wide quality improvement initiative to enhance care for pediatric patients with suspected sepsis, we developed a novel intervention using confidence-weighted testing to identify institutional areas of misinformation and knowledge gaps while also providing real-time feedback to individual learners. METHODS: We developed pediatric sepsis eLearning modules incorporating confidence-weighted testing. We distributed them to nurses, advanced practitioners, and physicians in emergency departments and acute care/non-intensive care unit inpatient settings in our hospital system. We analyzed completion and response data over 2 years following module distribution. Our outcomes included completion, confidently held misinformation (CHM; when a learner answers a question confidently but incorrectly), struggle (when a learner repeatedly answers a question incorrectly or with low confidence), and mastery (when a learner initially answers a question correctly and confidently). RESULTS: Eighty-three percent of assigned learners completed the modules (1,463/1,754). Although nurses had significantly more misinformation and struggled more than physicians and advanced practitioners, learners of all roles achieved 100% mastery as part of module completion. The greatest CHM and struggle were found in serum lactate interpretation's nuances and the hemodynamic shock states commonly seen in sepsis. CONCLUSIONS: Our novel application of confidence-weighted testing enhanced learning by correcting learners' misinformation. It also identified systems issues and institutional knowledge gaps as targets for future improvement.

An Acute Care Sepsis Response System Targeting Improved Antibiotic Administration.

BACKGROUND AND OBJECTIVES: Pediatric sepsis quality improvement in emergency departments has been well described and associated with improved survival. Acute care (non-ICU inpatient) units differ in important ways, and optimal approaches to improving sepsis processes and outcomes in this setting are not yet known. Our objective was to increase the proportion of acute care sepsis cases in our health system with initial antibiotic order-to-administration time ≤60 minutes by 20% from a baseline of 43% to 52% by December 2020. METHODS: Employing the Model for Improvement with broad stakeholder engagement, we developed and implemented interventions aimed at effective intervention for sepsis cases on acute care units. We analyzed process and outcome metrics over time using statistical process control charts. We used descriptive statistics to explore differences in antibiotic order-to-administration time and inform ongoing improvement. RESULTS: We cared for 187 patients with sepsis over the course of our initiative. The proportion within our goal antibiotic order-to-administration time rose from 43% to 64% with evidence of special cause variation after our interventions. Of all patients, 66% experienced ICU transfer and 4% died. CONCLUSIONS: We successfully decreased antibiotic order-to-administration time. We also introduced a novel model for sepsis response systems that integrates interventions designed for the complexities of acute care settings. We demonstrated impactful local improvements in the acute care setting where quality improvement reports and success have previously been limited.

Complement Activation Fragments Are Increased in Critically Ill Pediatric Patients with Severe AKI.

Background: Children who are critically ill with AKI suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in children who are critically ill. Methods: A biorepository of samples from children who are critically ill from a prior multisite study was leveraged to identify children with stage 3 AKI and matched to patients without AKI on the basis of PELOD-2 (illness severity) scores. Specimens were analyzed for plasma and urine complement activation fragments of factor B, C3a, C4a, and sC5b-9. The primary outcomes were MAKE30 and severe AKI rates. Results: In total, 14 patients with stage 3 AKI (five requiring RRT) were matched to 14 patients without AKI. Urine factor Ba and plasma C4a levels increased stepwise as severity of AKI increased, from no AKI to stage 3 AKI, to stage 3 AKI with RRT need. Plasma C4a levels were independently associated with increased risk of MAKE30 outcomes (OR, 3.2; IQR, 1.1-8.9), and urine Ba (OR, 1.9; IQR, 1.1-3.1), plasma Bb (OR, 2.7; IQR, 1.1-6.8), C4a (OR, 13.0; IQR, 1.6-106.6), and C3a (OR, 3.3; IQR, 1.3-8.4) were independently associated with risk of severe stage 2-3 AKI on day 3 of admission. Conclusions: Multiple complement fragments increase as magnitude of AKI severity increases. Very high levels of urine Ba or plasma C4a may identify patients at risk for severe AKI, hemodialysis, and MAKE30 outcomes. The fragments may be useful as a functional biomarker of complement activation and may identify those patients to study complement inhibition to treat or prevent AKI in children who are critically ill. These findings suggest the need for further specific investigations of the role of complement activation in children who are critically ill and at risk of AKI.

Elevated Heart Rate and Risk of Revisit With Admission in Pediatric Emergency Patients.

OBJECTIVE: The aim of this study was to identify emergency department (ED) heart rate (HR) values that identify children at elevated risk of ED revisit with admission. METHODS: We performed a retrospective cohort study of patients 0 to 18 years old discharged from a tertiary-care pediatric ED from January 2013 to December 2014. We created percentile curves for the last recorded HR for age using data from calendar year 2013 and used receiver operating characteristic (ROC) curves to characterize the performance of the percentiles for predicting ED revisit with admission within 72 hours. In a held-out validation data set (calendar year 2014 data), we evaluated test characteristics of last-recorded HR-for-age cut points identified as promising on the ROC curves, as well as those identifying the highest 5% and 1% of last recorded HRs for age. RESULTS: We evaluated 183,433 eligible ED visits. Last recorded HR for age had poor discrimination for predicting revisit with admission (area under the curve, 0.61; 95% confidence interval, 0.58-0.63). No promising cut points were identified on the ROC curves. Cut points identifying the highest 5% and 1% of last recorded HRs for age showed low sensitivity (10.1% and 2.5%) with numbers needed to evaluate of 62 and 50, respectively, to potentially prevent 1 revisit with admission. CONCLUSIONS: Last recorded ED HR discriminates poorly between children who are and are not at risk of revisit with admission in a pediatric ED. The use of single-parameter HR in isolation as an automated trigger for mandatory reevaluation prior to discharge may not improve revisit outcomes.

Pediatric Sepsis in Community Emergency Care Settings: Guideline Concordance and Outcomes.

OBJECTIVES: Bundled pediatric sepsis care has been associated with improved outcomes in tertiary pediatric emergency departments. Sepsis care at nontertiary sites where most children seek emergency care is not well described. We sought to describe the rate of guideline-concordant care, and we hypothesized that guideline-concordant care in community pediatric emergency care settings would be associated with decreased hospital length of stay (LOS). METHOD: This retrospective cohort study of children with severe sepsis presenting to pediatric community emergency and urgent care sites included children 60 days to 17 years with severe sepsis. The primary predictor was concordance with the American College of Critical Care Medicine 2017 pediatric sepsis resuscitation bundle, including timely recognition, vascular access, intravenous fluids, antibiotics, vasoactive agents as needed. RESULTS: From January 1, 2015, to December 31, 2017, 90 patients with severe sepsis met inclusion criteria; 22 (24%) received guideline-concordant care. Children receiving concordant care had a median hospital LOS of 95.3 hours (50.9-163.8 hours), with nonconcordant care, LOS was 88.3 hours (57.3-193.2 hours). In adjusted analysis, guideline-concordant care was not associated with hospital LOS (incident rate ratio, 0.99 [0.64-1.52]). The elements that drove overall concordance were timely recognition, achieved in only half of cases, vascular access, and timely antibiotics. CONCLUSIONS: Emergency care for pediatric sepsis in the community settings studied was concordant with guidelines in only 24% of the cases. Future study is needed to evaluate additional drivers of outcomes and ways to improve sepsis care in community emergency care settings.

Using an eLearning Module to Facilitate Sepsis Knowledge Acquisition Across Multiple Institutions and Learner Disciplines.

OBJECTIVE: Guidelines exist for care of pediatric sepsis, but no study has assessed the benefit of electronic learning (eLearning) in this topic area. The objective of this multicenter study was to assess knowledge acquisition and retention for pediatric sepsis across multiple health care provider roles, using an adaptive and interactive eLearning module. METHODS: The study used pretest, posttest, and 90-day delayed test scores to evaluate provider knowledge after an adaptive and interactive eLearning module intervention. The eLearning module contained conditional logic-based assessments that allowed real-time adjustments of the displayed content according to each participant's demonstrated knowledge. Physicians, nurses, and advanced practice providers, primarily emergency department based, at 9 pediatric institutions were included. Changes in test scores were stratified by provider role. RESULTS: A total of 574 participants completed the posttest, and 296 (51.6%) of those completed the delayed test. Across all providers, there was an increase in test scores of 15.7% between the pretest and posttest (P < 0.001) with a large effect size as measured by Cramer's V. Across all providers, there was an overall test score increase of 5.2% (P < 0.001) between the pretest and delayed test, with a small effect size. CONCLUSIONS: An eLearning module improved immediate and delayed pediatric sepsis knowledge in pediatric health care providers across multiple institutions and provider roles. Immediate knowledge gain was meaningful as indicated by effect sizes, although by the time of the delayed test, the effect was smaller. This module fills an important gap in currently available pediatric sepsis education.

Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes.

Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.